Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions

Aging is one of the global challenges of our time. The search for new anti-aging interventions is also an issue of great actuality. We report on the success of Drosophila melanogaster lifespan extension under the combined influence of dietary restriction, co-administration of berberine, fucoxanthin, and rapamycin, photodeprivation, and low-temperature conditions up to 185 days in w1118 strain and up to 213 days in long-lived E(z)/w mutants. The trade-off was found between longevity and locomotion. The transcriptome analysis showed an impact of epigenetic alterations, lipid metabolism, cellular respiration, nutrient sensing, immune response, and autophagy in the registered effect.

Supplementary Figure 5. Comparison of total lipid content in different sexes of E(z)/w and w/w lines exposed to the combined action of dietary restriction, co-administration of berberine, fucoxanthin, and rapamycin, constant darkness, and low temperature (18°C) conditions. Each data point represents a mean of 8-12 biological replicates ±SEM. *p<0.05 differences between the agematched adult flies of E(z)/w and w/w lines.
Supplementary Figure 8. Dotplots showing the results of KEGG pathways enrichment analyses performed for DE genes (either up-regulated or down-regulated) associated with exposure to combination of anti-aging interventions (dietary restriction (DR); co-administration of berberine, fucoxanthin, and rapamycin (3G); living in constant darkness (DD) and low temperature (18°C) conditions) in 50-day-old D. melanogaster. (a) w/w males, (b) w/w females, (c) E(z)/w males, (d) E(z)/w females. The x-axis and dot size indicate gene ratio (the number of DE genes involved in the KEGG pathway divided by total number of genes that are annotated as participants of this pathway). Dot color indicates the enrichment test FDR (false discovery rate) according to Fisher's exact test.
Supplementary   GTgenotype, CONDcombination of experimental conditions (maintaining in the dark, low ambient temperature, a combination of rapamycin, berberine, and fucoxanthin, and dietary restriction), P(M)prior model probability, P(M|data)posterior model probabilities, BFMchange from prior odds to posterior odds for each model, BF10 -Bayes factor.
Supplementary GT -genotype, CONDcombination of experimental conditions (maintaining in the dark, low ambient temperature, a combination of rapamycin, berberine, and fucoxanthin, and dietary restriction), P(M)prior model probability, P(M|data)posterior model probabilities, BFMchange from prior odds to posterior odds for each model, BF10 -Bayes factor.
Supplementary    GT -E(z)/w genotype, CONDcombination of experimental conditions (maintaining in the dark, low ambient temperature, a combination of rapamycin, berberine, and fucoxanthin, and dietary restriction), P(M)prior model probability, P(M|data)posterior model probabilities, BFMchange from prior odds to posterior odds for each model, BF10 -Bayes factor. The most probable models are in bold.